The overall goals of this proposal are: To define the role of vitamin A and its precursors and derivatives in the prevention and treatment of human cancer. Our approaches involve a multidisciplinary clinical science- oriented cancer research effort and involve: 1) The use of two well-defined biological systems to determine - interaction of retinoids and carotenoids with ultraviolet light B-induced tumorigenesis and the immune system in mice. - effective combinations of retinoids with other biological modifiers using a clonogenic human tumor cell system. 2) Development of two new human models for prevention - biological and biochemical characterization of Barrett's esophagus as a preneoplastic model for adenocarcinoma. - epidemiologic and nutritional characterization of individuals at high risk for non-melanoma skin cancer. 3) Determination of the efficacy of retinoids as anticancer agents in several distinct settings - to continue clinical investigations of retinoids as treatment for selected preneoplastic and neoplastic disease states. - to continue our double-blind stratified and randomized control study in the chemoprevention of patients at high risk of relapse for skin cancer: 13-cis retinoic acid vs retinol vs placebo. These complex interrelated chemoprevention and therapeutic investigations will be administered and processed through administrative and biometry cores designed to produce maximum utilization of data and information.